Epithelium and fibroblast-like phenotypes derived from HPV16 E6/E7-immortalized human gingival keratinocytes following chronic ethanol treatment

Chamulitrat, Waleé; Schmidt, Rainer; Chunglok, Warangkana; Kohl, Annette; Tomakidi, Pascal

doi:10.1078/0171-9335-00317

Cited by 33 publications

(39 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, our results show that functional RANKL can also be derived directly from prostate cancer cells along with their osteomimetic properties, and thus contribute to increased bone turnover and cancer cell growth, survival and migration in bone [8]. There remain some discrepancies regarding to the expression of RANKL by prostate cancer cells, since previous reports by others have shown that bone metastatic cancer cell lines lack RANKL expression [31][32][33], consistent with the view that in osteolytic bone metastasis RANKL is osteoblast-derived and is induced by cancer cell-derived PTHrP [30,32]. However, we have recently conducted multiplexed quantum dot analysis of RANKL expression in clinical human prostate cancer bone metastatic specimens.…”

Section: Resultscontrasting

confidence: 57%

Epithelial to mesenchymal transition (EMT) in human prostate cancer: lessons learned from ARCaP model

Zhau

Odero-Marah

Lue

et al. 2008

Clin Exp Metastasis

135

156

View full text Add to dashboard Cite

Androgen refractory cancer of the prostate (ARCaP) cells contain androgen receptor (AR) and synthesize and secrete prostate specific antigen (PSA). We isolated epithelia-like ARCaP(E) from parental ARCaP cells and induced them to undergo epithelial-mesenchymal transition (EMT) by exposing these cells to soluble factors including TGFbeta1 plus EGF, IGF-1, beta2-microglobulin (beta2-m), or a bone microenvironment. The molecular and behavioral characteristics of the resultant ARCaP(M) were characterized extensively in comparison to the parental ARCaP(E) cells. In addition to expressing mesenchymal biomarkers, ARCaP(M) gained 100% incidence of bone metastasis. ARCaP(M) cells express receptor activator of NF-kappaB ligand (RANKL), which was shown to increase tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in culture, and when metastatic to bone in vivo. We provide evidence that RANKL expression was promoted by increased cell signaling mediated by the activation of Stat3-Snail-LIV-1. RANKL expressed by ARCaP(M) cells is functional both in vitro and in vivo. The lesson we learned from the ARCaP model of EMT is that activation of a specific cell signaling pathway by soluble factors can lead to increased bone turnover, mediated by enhanced RANKL expression by tumor cells, which is implicated in the high incidence of prostate cancer bone colonization. The ARCaP EMT model is highly attractive for developing new therapeutic agents to treat prostate cancer bone metastasis.

show abstract

Section: Resultscontrasting

confidence: 57%

Epithelial to mesenchymal transition (EMT) in human prostate cancer: lessons learned from ARCaP model

Zhau

Odero-Marah

Lue

et al. 2008

Clin Exp Metastasis

135

156

View full text Add to dashboard Cite

show abstract

“…We measured the expression of epithelial markers, such as Krt14 (Chamulitrat et al, 2003;Ke et al, 2008) and Bves (Wada et al, 2001), by qRT-PCR (Fig. 2C).…”

Section: Loss Of Nf1 Results In Spontaneous Emt Of Epicardial Cells Imentioning

confidence: 99%

Nf1 limits epicardial derivative expansion by regulating epithelial to mesenchymal transition and proliferation

Baek

Tallquist

2012

Development

View full text Add to dashboard Cite

The epicardium is the primary source of coronary vascular smooth muscle cells (cVSMCs) and fibroblasts that reside in the compact myocardium. To form these epicardial-derived cells (EPDCs), the epicardium undergoes the process of epithelial to mesenchymal transition (EMT). Although several signaling pathways have been identified that disrupt EMT, no pathway has been reported that restricts this developmental process. Here, we identify neurofibromin 1 (Nf1) as a key mediator of epicardial EMT. To determine the function of Nf1 during epicardial EMT and the formation of epicardial derivatives, cardiac fibroblasts and cVSMCs, we generated mice with a tissue-specific deletion of Nf1 in the epicardium. We found that mutant epicardial cells transitioned more readily to mesenchymal cells in vitro and in vivo. The mesothelial epicardium lost epithelial gene expression and became more invasive. Using lineage tracing of EPDCs, we found that the process of EMT occurred earlier in Nf1 mutant hearts, with an increase in epicardial cells entering the compact myocardium. Moreover, loss of Nf1 caused increased EPDC proliferation and resulted in more cardiac fibroblasts and cVSMCs. Finally, we were able to partially reverse the excessive EMT caused by loss of Nf1 by disrupting Pdgfrα expression in the epicardium. Conversely, Nf1 activation was able to inhibit PDGF-induced epicardial EMT. Our results demonstrate a regulatory role for Nf1 during epicardial EMT and provide insights into the susceptibility of patients with disrupted NF1 signaling to cardiovascular disease.

show abstract

“…In addition to stimulating proliferation of epithelial cells, EGF is a well-recognized motogenic factor and has been implicated in the migration of squamous carcinoma cells (22,23) and exposure of HN12 cells to EGF also enhances vimentin expression (14) and motility (15). Using a model system of human papillomavirus-immortalized gingival keratinocytes, Chamulitrat et al (24) found that exposure to ethanol, an etiologic factor for oral carcinogenesis, resulted in a switch to a vimentinpositive cell phenotype and was associated with a spindle Transition from an epithelial to a mesenchymal phenotype is not only associated with expression of vimentin but also with altered expression of differentiation-specific keratins. Dysregulation of keratin expression has long been recognized as a feature of epithelial tumor progression (25).…”

Section: Discussionmentioning

confidence: 99%

Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility

Paccione

Miyazaki

Patel

et al. 2008

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

At later stages of tumor progression, epithelial carcinogenesis is associated with transition to a mesenchymal phenotype, which may contribute to the more aggressive properties of cancer cells and may be stimulated by growth factors such as epidermal growth factor and transforming growth factor-B. Previously, we found that cells derived from a nodal metastatic squamous cell carcinoma are highly proliferative and motile in vitro and tumorigenic in vivo. In the current study, we have investigated the role of vimentin in proliferation and motility. Cells derived from nodal metastasis express high levels of vimentin, which is undetectable in tumor cells derived from a synchronous primary lesion of tongue. Vimentin expression was enhanced by epidermal growth factor and transforming growth factor-B both independently and in combination. Use of RNA interference resulted in the generation of stable cell lines that express constitutively low levels of vimentin. RNA interference-mediated vimentin knockdown reduced cellular proliferation, migration, and invasion through a basement membrane substitute by 3-fold compared with nontargeting controls. In addition, cells with reduced vimentin reexpressed differentiation-specific keratins K13, K14, and K15 as a result of increased gene transcription as judged by quantitative PCR and promoterreporter assays. Furthermore, cells in which vimentin expression was reduced showed a greatly decreased tumorigenic potential, as tumors developing from these cells were 70% smaller than those from control cells. The data suggest that reversal of the mesenchymal phenotype by inhibiting vimentin expression results in reexpression of epithelial characteristics and reduced tumor aggressiveness. [Mol Cancer Ther 2008;7(9):2894 -903]

show abstract

Epithelium and fibroblast-like phenotypes derived from HPV16 E6/E7-immortalized human gingival keratinocytes following chronic ethanol treatment

Cited by 33 publications

References 42 publications

Epithelial to mesenchymal transition (EMT) in human prostate cancer: lessons learned from ARCaP model

Epithelial to mesenchymal transition (EMT) in human prostate cancer: lessons learned from ARCaP model

Nf1 limits epicardial derivative expansion by regulating epithelial to mesenchymal transition and proliferation

Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility

Contact Info

Product

Resources

About